Postoperative Adjuvant Therapy With Recombinant Interferon-Alpha Following Curative Resection of Hepatocellular Carcinoma: a Randomized Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 主要终点
- Occurrence of recurrent disease
研究概览
简要总结
We conducted a randomized controlled trial of adjuvant interferon therapy in patients with predominantly hepatitis B-related hepatocellular carcinoma (HCC) to investigate whether the prognosis after hepatic resection could be improved. Since February 1999, patients with no residual disease after hepatic resection for HCC were randomly assigned with stratification by pTNM stage to receive no treatment (control group), interferon alpha-2b 10 MIU/m2 (IFN-I group) or 30 MIU/m2 (IFN-II group) thrice weekly for 16 weeks. Enrollment to the IFN-II group was terminated from January 2000 because adverse effects resulted in treatment discontinuation in the first 6 patients. By June 2002, 40 patients each had been enrolled into the control group and IFN-I group. The baseline clinical, laboratory and tumor characteristics of both groups were comparable. The 1- and 5-year survival rates were 85% and 61%, respectively for the control group and 97% and 79%, respectively for the IFN-I group (P=0.137). After adjusting for the confounding prognostic factors in a Cox model, the relative risk of death for interferon treatment was 0.42 (95% CI 0.17 - 1.05; P=0.063). Exploratory subset analysis showed that adjuvant interferon had no survival benefit for pTNM stage I/II tumor (5-year survival 90% in both groups; P=0.917) but prevented early recurrence and improved the 5-year survival of patients with stage III/IVA tumor from 24% to 68% (P=0.038). In conclusion, in a group of patients with predominantly hepatitis B-related HCC, adjuvant interferon therapy prevented early recurrence and improved survival in those with pTNM stage III/IVA tumors.
详细描述
- Background
Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death in Hong Kong and the majority are hepatitis B related. Hepatic resection has remained the only therapeutic option that can offer these patients a chance of long-term survival. Although the safety of hepatectomy has improved, postoperative recurrences are frequent. Depending on the size of the primary tumors, recent reports from Japan, France and Hong Kong1 showed that the postoperative recurrence rate was 20 to 64% at one year and 57 to 81% at 3 years.
While the hepatic remnant is the predominant site of recurrence, involvement of extrahepatic organs was not infrequent. There are three possible mechanisms for the development of recurrent disease:
i) residual tumor cells due to an inadequate resection margin ii) subclinical metastasis that occurs before or during hepatic resection iii) metachronous multicentric hepatocarcinogenesis which may be related to the underlying necroinflammation of chronic active hepatitis and oncogenic activities of hepatitis viruses.
The surgeon's attempt to prevent recurrence by more extensive resection is prohibited by the need to preserve hepatic function. Futhermore, even a major hepatic resection cannot guarantee freedom from recurrence since metachronous multicentric tumors can develop in the entire liver. Theorectically, total hepatectomy and liver transplantation removes both the subclinical metastases in the liver and prevent metachronous lesions. Unfortunately, with immunosuppressive therapy, recurrences are frequent and tumors grow more rapidly, thus, illustrating the importance of the host immune surveillance in preventing the development of recurrence.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All patients who undergo a curvative hepatic resection for HCC at the Department of Surgery, Queen Mary Hospital are included. The criteria for curative resection include all of the following :
- •i) Complete extirpation of disease as demonstrated by intraoperative ultrasonography during surgery ii) Histologic evidence of a clear resection margin iii) No evidence of residual disease in the liver remnant as demonstrated by spiral contrast-enhanced CT scan one month after surgery
排除标准
- •i) patient refusal ii) age > 75 years old iii) hospital mortality iv) disease previously treated by regional or systemic chemotherapy, hormonal therapy or immunotherapy v) poor hepatic function:
- •presence of hepatic encephalopathy
- •presence of ascites not controlled by diuretics
- •history of variceal bleeding within last 3 months
- •total serum bilirubin > 50 umol/L
- •serum albumin < 30 g/L
- •prothrombin time prolonged for > 4 seconds vi) poor renal function with serum creatinine > 180mol/L vii) Absolute neutrophil count < 1.5 x 109/L viii) Platelet count < 75 x 109/L ix) poor performance status with European Cooperative Oncology Group (ECOG) scale grade III or IV
结局指标
主要结局
Occurrence of recurrent disease
次要结局
- Death of the patient